AP26113 is an experimental drug of a targeted small molecular tyrosine kinase inhibitor developed by the Ariad Pharmaceuticals Company, and is used for treating patients suffering from anaplastic lymphoma kinase positive (ALK) metastatic nonsmall cell lung cancer (NSCLC) which resists crizotinib. The drug was granted as a breakthrough therapy drug by Food and Drug Administration (FDA) in August 2014. According to clinical data at present, AP26113 has continuous anti-tumor activity on patients suffering from the ALK positive nonsmall cell lung cancer, including brain metastases patients. Moreover, the inhibitory activity of AP26113 to ALK is about 10 times of the inhibitor activity of the crizotinib to ALK, and all nine identified crizotinib resistant ALK mutation can be inhibited.
The chemical name of AP26113 is 5-chloro-N2-[4-[4-(dimethyl amino)-1-piperidyl]-2-methoxyphenyl]-N4-[2-(dimethyl phosphitylate)phenyl]-2,4-diaminopyrimidine (I), and a structural formula thereof is as follows:

A preparation method for AP26113 has been researched and reported, and PCT patent WO2009143389 of the Ariad Company and United States patents US20130225527, US20130225528 and US20140066406 have reported a preparation method for AP26113 and raw materials A and B therefor. According to the method, 2,4,5-trichloropyrimidine and the raw material A are subjected to substitution reaction on a pyrimidine ring and then the 2,4,5-trichloropyrimidine and the raw material B are subjected to substitution reaction on the pyrimidine ring to obtain the target compound AP26113.

By analysis of the above synthetic routes, although synthetic steps are simple comparatively, difference of nucleophilic activities of three helium atoms on the 2,4,5-trichloropyrimidine is limited, the regioselectivity is inevitably interfered in the face of the same or similar anilines groups, unnecessary side reactions are caused, and thus, the quality of a product is affected. Meanwhile, by use of a precious metal palladium reagent in a reaction process, the manufacturing cost is increased to some extent, and industrialization is not facilitated.
Therefore, use of a modern synthetic technology, use of easily-obtained raw materials, design and development of a simple, speedy, economical and environment-friendly new synthetic route which facilitates industrialization, and particularly overcoming of side reactions caused by regioselectivity on the pyrimidine ring play an important role in economic and technical development of the drug.